The 3-amino-2-hydroxy-l-propyl ethers have been prepared by reacting a corresponding alcohol with an epoxy compound, such as epichlorohydrin or glycidyl p-toluenesulfonate to prepare a glycidyl aryl ether and reacting it with an amine. The reaction of the alcohol with epichlorohydrin or glycidyl p-toluenesulfonate is carried out in the presence of an alkali metal base, such as sodium hydride or sodium hydroxide, or an organic base, such as triethylamine or pyridine. However, in case of carrying out in the base, the epoxy compound, such as epichlorohydrin must be used in excess and therefore, the reaction is not economical. In case of using a strong base, such as sodium hydride, there is a possibility of burning in the post treating. Furthermore, in case of using an aryl derivative having a substituent unstable in basic conditions, the yield is not good.
By the way, 3-amino-2-hydroxy-1-propyl ethers have an asymmetric carbon atom and exist in optical isomers. Recently in developing medicines comprising optical isomers, each isomer is investigated. Therefore, it becomes very important to establish a method to prepare easily an optically active compound with highly optical purity of these compounds. In order to solve such problems, combinations of many kinds of bases with an optically active epichlorohydrin, glycidyl p-toluenesulfonate, or glycidyl m-nitrobenzenesulfonate have been investigated.
These methods, for instance, are described in Japanese Patent Publication No. 1-121282, Japanese Patent Publication No. 1-279890, Japanese Patent Publication No. 1-279887, European Patent No. 454385, Japanese Patent Publication B No. 6-37449, Chem. Pharm. Bull., 35, 8691 (1987), Chem. Pharm. Bull., 38, 2092 (1990), J. Org. Chem., 54, 1295 (1989) and so on.
However, in all these methods, marked racemization occurs on the reaction and the optical purity decreases.
Optical purity of an 3-amino-2-hydroxy-1-propyl ether prepared by reacting p-hydroxyphenylacetoamide and an optically active epichlorohydrin in sodium hydroxide as a base to prepare a glycidyl ether and then reacting it with diisopropylamine decreases to 90% e.e. and it is not satisfactory.
The present inventors engaged extensively in solving above problems, and found to prepare easily and with good yield an object compound of the formula (4) below by reacting an epoxy compound of the formula (1) below and an alcohol of (2) below in the presence of a fluoride salt and then, reacting it with an amine of the formula (3) below. Furthermore, when an optically active epoxy compound (1) is used, the object compound obtained is also optically active, and any marked racemization does not occur on the reaction. When an epoxy compound with highly optical purity is used, there is obtained an 3-amino-2-hydroxy-1-propyl ether with highly optical purity.